蓝莓在创伤后应激障碍(PTSD)动物模型中的抗炎作用。
The Anti-Inflammatory Effects of Blueberries in an Animal Model of Post-Traumatic Stress Disorder (PTSD).
作者信息
Ebenezer Philip J, Wilson C Brad, Wilson Leslie D, Nair Anand R, J Francis
机构信息
Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University Baton Rouge, Louisiana, United States of America.
Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University Baton Rouge, Louisiana, United States of America.
出版信息
PLoS One. 2016 Sep 7;11(9):e0160923. doi: 10.1371/journal.pone.0160923. eCollection 2016.
Post-traumatic stress disorder (PTSD) is a trauma and stressor-related disorder that results in a prolonged stress response. It is associated with increased oxidative stress and inflammation in the prefrontal cortex (PFC) and hippocampus (HC). The only approved therapy for PTSD is selective serotonin re-uptake inhibitors (SSRIs), but their efficacy is marginal. Recently, we demonstrated that over-production of norepinephrine (NE) as the possible reason for the lack of efficacy of SSRIs. Hence, there is a need for novel therapeutic approaches for the treatment of PTSD. In this study, we investigated the anti-inflammatory role of blueberries in modulating inflammatory markers and neurotransmitter levels in PTSD. Rats were fed either a blueberry enriched (2%) or a control diet. Rats were exposed to cats for one hour on days 1 and 11 of a 31-day schedule to simulate traumatic conditions. The rats were also subjected to psychosocial stress via daily cage cohort changes. At the end of the study, the rats were euthanized and the PFC and HC were isolated. Monoamines were measured by high-performance liquid chromatography. Reactive oxygen species (ROS), gene and protein expression levels of inflammatory cytokines were also measured. In our PTSD model, NE levels were increased and 5-HT levels were decreased when compared to control. In contrast, a blueberry enriched diet increased 5-HT without affecting NE levels. The rate limiting enzymes tyrosine hydroxylase and tryptophan hydroxylase were also studied and they confirmed our findings. The enhanced levels free radicals, gene and protein expression of inflammatory cytokines seen in the PTSD group were normalized with a blueberry enriched diet. Decreased anxiety in this group was shown by improved performance on the elevated plus-maze. These findings indicate blueberries can attenuate oxidative stress and inflammation and restore neurotransmitter imbalances in a rat model of PTSD.
创伤后应激障碍(PTSD)是一种与创伤和应激源相关的疾病,会导致长期的应激反应。它与前额叶皮质(PFC)和海马体(HC)中氧化应激和炎症的增加有关。PTSD唯一被批准的治疗方法是选择性5-羟色胺再摄取抑制剂(SSRI),但其疗效有限。最近,我们证明去甲肾上腺素(NE)的过量产生可能是SSRI疗效不佳的原因。因此,需要新的治疗方法来治疗PTSD。在本研究中,我们研究了蓝莓在调节PTSD炎症标志物和神经递质水平方面的抗炎作用。给大鼠喂食富含蓝莓(2%)的饮食或对照饮食。在31天的实验周期中,于第1天和第11天将大鼠暴露于猫前1小时以模拟创伤情况。大鼠还通过每日更换笼舍同伴遭受心理社会应激。在研究结束时,对大鼠实施安乐死并分离出PFC和HC。通过高效液相色谱法测量单胺类物质。还测量了活性氧(ROS)、炎症细胞因子的基因和蛋白质表达水平。在我们的PTSD模型中,与对照组相比,NE水平升高而5-羟色胺(5-HT)水平降低。相比之下,富含蓝莓的饮食增加了5-HT水平而不影响NE水平。我们还研究了限速酶酪氨酸羟化酶和色氨酸羟化酶,它们证实了我们的研究结果。PTSD组中自由基水平升高、炎症细胞因子的基因和蛋白质表达,通过富含蓝莓的饮食恢复正常。该组在高架十字迷宫实验中表现改善,表明焦虑减轻。这些发现表明,蓝莓可以减轻氧化应激和炎症,并恢复PTSD大鼠模型中的神经递质失衡。
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